THE 3-DIMENSIONAL QUESTION - CAN CLINICALLY RELEVANT TUMOR DRUG-RESISTANCE BE MEASURED IN-VITRO

In vivo-like drug responses are observed in three-dimensional culture but frequently not in two-dimensional culture, indicating that drug re sponse may be a function of tissue architecture. Alexis Carrel introdu ced that in vitro culture of tissues in the beginning of the century u tilizing a culture system that allowed the three-dimensional growth of tissues. Leighton improved upon this system by developing a substrate of sponge matrices. Other methods of three-dimensional culture includ e collagen gels and what are known as organ culture systems on filters or meshes. In addition, cell suspensions can be converted into multic ellular spheroids, another form of three-dimensional culture. Comparis on of the three-dimensional culture methods with two-dimensional cultu re methods has shown critical differences in drug response. The in viv o mechanism of drug resistance may involve alterations in cell-cell in teraction which may occur in three-dimensional culture as opposed to m onolayer culture.